This is a Major Research Program responding to the announcement in the NIH Guide, Vol. 5, No. 8, June 25, 1976, National Institute of Child Health and Human Development Request for Application. The goals of this Major Research Program are to provide better methods for the detection and assessment of fetal hypoxia and to determine the ways in which smoking adversely affects the fetus. The cardiovascular, respiratory and biochemical responses of the fetus to both hypoxia and smoking will be studied during development. In order to gain an insight into the mechanisms involved in these responses, parallel observations will be made in both the human fetus and the chronically instrumented subhuman primate in which direct measurements of biochemical and biophysical parameters can be made. The process of activation of the fetal pituitary in response to hypoxia will be studied to define specific and novel hormonal markers of hypoxic stress. The effects of autonomic mediators on electrophysical characteristics of the developing heart will be studied in the presence of hypoxia and acidosis. Mathematical models will be developed for the prediction of outcome through synthesizing data from animal experiments with clinical information derived during labor and delivery. The structure and composition of the placenta in association with smoking during pregnancy will be characterized. The type of growth retardation caused by smoking, the timing of this effect, and the potential for the fetus to recover will be determined.